PF-07265028 As Single Agent And In Combination With Sasanlimab in Advanced or Metastatic Solid Tumors

JRCT ID: jRCT2031210676

Registered date:18/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: *Advanced Solid Tumors *Gastric Cancer *Gastroesophageal Junction Cancer *(and 3 more...)
• Date of first enrollment: 28/03/2022
• Target sample size: 240
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

Drug: PF-07265028
PF-07265028 will be administered orally

Drug: PF-07265028
PF-07265028 will be administered orally
Biological: Sasanlimab
Administered subcutaneously
Other Name: PF-06801591

Outcome(s)

Primary Outcome

Primary Outcome Measures :
1.Number of participants with Dose-limiting toxicities (DLTs) in Dose Escalation (Part 1) [ Time Frame: Cycle 1 (28 days) ]
DLTs will be evaluated during Cycle 1 (a cycle is 28 days) in Part 1. The number of DLTs will be used to determine the optimal dose
2.Number of participants with adverse events (AEs) [ Time Frame: Baseline through up to 2 years ]
AEs characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 5.0), timing, seriousness, and relationship to study therapy.
3.Number of participants with clinically significant laboratory abnormalities [ Time Frame: Baseline through up to 2 years ]
Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.
4.Objective response rate (ORR) in Dose Expansion (Part 2) [ Time Frame: Baseline through up to 2 years or until disease progression ]
Tumor response based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary Outcome

Secondary Outcome Measures :
1.The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Cmax. [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Maximum observed plasma concentration of PF-07265028 (Cmax) and Maximum observed steady state plasma concentration (Cmax, ss)
2.The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through Tmax. [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Time to maximal observed plasma concentration of PF-07265028 (Tmax) and Time to reach Maximum Observed Steady State Plasma Concentration (Tmax,ss).
3.The pharmacokinetic profile of single and multiple doses PF-07265028 alone and in combination with sasanlimab through AUC [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 and area under the curve within one dose interval at steady state (AUCtau,ss)
4.The effect of food on the pharmacokinetic profile of PF-07265028 through Cmax. [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Maximum observed plasma concentration of PF-07265028 (Cmax) under fasted and fed conditions in the subset of participants
5.The effect of food on the pharmacokinetic profile of PF-07265028 through Tmax [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Time to maximal observed plasma concentration of PF-07265028 (Tmax) under fasted and fed conditions in the subset of participants
6.The effect of food on the pharmacokinetic profile of PF-07265028 through AUC [ Time Frame: Days 1, 8, 15, 16 and 22 of Cycle 1 (each cycle is 28 days) ]
Area under the concentration versus time curve from time zero to the last quantifiable time point prior to the next dose (AUClast) of PF-07265028 under fasted and fed conditions in the subset of participants
7.The pharmacokinetic profile of sasanlimab when given in combination with PF-07265028 through Cmin [ Time Frame: Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) ]
Minimum plasma concentration (Cmin) will be calculated through the measured pre-dose plasma concentration
8.The immunogenicity of sasanlimab when given in combination with PF-07265028 through ADA and NAb [ Time Frame: Day 1 of cycle 1 (each cycle is 28 days), Day 1 of cycle 2, Day 1 of cycle 3, Day 1 of cycle 5 and thereafter every 6 cycles (each cycle is 28 days) ]
Incidence and titers of anti-drug antibodies (ADA) and neutralizing antibodies (NAb) against sasanlimab
9.The effect of PF-07265028 alone and in combination with sasanlimab on tumor immune biomarkers modulation [ Time Frame: Baseline through up to 2 years ]
Levels of intratumor T cells and PD-L1 expression in pre- and post-treatment tumor biopsies
10.ORR in Dose Escalation (Part 1) [ Time Frame: From baseline through disease progression or study completion (approximately 2 years) ]
Tumor response assessment based on RECIST 1.1
11.Time to event endpoints (DOR) in Dose Expansion (Part 2) [ Time Frame: From baseline through disease progression or study completion (approximately 2 years) ]
Duration of response (DOR) as assessed using RECIST 1.1.
12.Time to event endpoints (PFS) in Dose Expansion (Part 2) [ Time Frame: From baseline through disease progression or study completion (approximately 2 years) ]
Progression free survival (PFS) as assessed using RECIST 1.1.
13.Time to event endpoints (OS) in Dose Expansion (Part 2) [ Time Frame: From baseline through disease progression or study completion (approximately 2 years) ]
Overall survival (OS) assessed proportion of patients alive

Key inclusion & exclusion criteria

• Age minimum: >= 20age old
• Age maximum: <= 99age old
• Gender: Both

Include criteria

Key Inclusion Criteria:
Across all cohorts:
1.Eastern Cooperative Oncology Group (ECOG) performance status <=1
2.Adequate hematological, kidney and liver function
3.Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
4.Resolved acute effects of any prior therapy
5.All participants must provide archival formalin-fixed paraffin-embedded (FFPE) tumor tissue:
Part 1: If archival sample is older than 6 months, the participant must consent to undergo a fresh biopsy during the screening.
Part 2 Fresh tumor biopsy during screening is required unless there is archival tissues less than 3 months old and subsequent to the last systemic anti-cancer therapy.
Part 1A Monotherapy:
Histologically or cytologically confirmed advanced or metastatic solid tumors which have progressed following systemic anticancer therapies, or are resistant to standard therapy or for which no standard therapy is available, or for whom standard therapy is not tolerated.
Part 1B Combination Therapy:
Histologically or cytologically confirmed advanced or metastatic solid tumor which have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor.
Part 2 Dose Expansion:
Histologically or cytologically confirmed advanced or metastatic malignancies, including gastric/Gastroesophageal junction cancer, Head and neck squamous cell carcinoma, or urothelial cancer (non-small cell lung cancer and other solid tumors may be included) who have progressed following systemic anticancer therapies, including at least 1 checkpoint inhibitor

Exclude criteria

Key Exclusion Criteria:
1.Participants with any other active malignancy within 3 years prior to enrollment
2.Participants with active autoimmune conditions or history of autoimmune diseases that may relapse
3.History of interstitial lung disease, pneumonitis (non-infectious) or uncontrolled lung diseases
4.History of prior immune-related adverse events (irAEs) Grade >=3
5.Central nervous system metastases
6.Significant cardiac or pulmonary conditions or events within previous 6 months
7.Active, uncontrolled bacterial, fungal, or viral infection
8.Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PF-07265028

Related Information

• Primary Sponsor: Kawai Norisuke
• Secondary ID(s): NCT05233436